Dorothy Schafer
University of Massachusetts Chan Medical School, MA·Neuroscience
The brain constantly rewires and repairs itself, and much of this work is done by glia, the non-neuron cells that make up about half of all brain cells. Two kinds matter most here.
- Fields
Neuroscience
Microbiology & Immunology
- Topics
microglia
astrocytes
synapse remodeling
- Grants
- 2 known grants, through May 2031
What they work on
- Determine whether microglia or other macrophages account for the reduced inflammation and improved remyelination seen in mice lacking UNC93B1, the chaperone eTLRs need, in acute and immune-mediated demyelination models.
- Define the trigger that activates eTLRs, such as TLR13, which senses single-stranded RNA, in demyelinating lesions and drives neuroinflammation and impaired remyelination, using cell-specific genetic manipulation in mice.
- Dissect the downstream signaling that lets eTLR-deficient mice remyelinate better after cuprizone or LPC-induced demyelination, which damage myelin and serve as mouse models.
- Define the developmental window in which CX3CL1-CX3CR1 (fractalkine) signaling drives microglial engulfment of thalamocortical synapses and astrocyte wrapping of synapses in the mouse barrel cortex after whisker removal.
- Test whether astrocyte wrapping of synapses limits microglia-dependent synapse removal in the barrel cortex, and whether microglia use Wnt signaling to control this wrapping, using cell-specific genetic approaches.
More about the research
Microglia are the brain's resident immune cells and clean up debris. Astrocytes are star-shaped support cells that wrap around connections between neurons. The lab asks how these cells decide what to remove and when cleanup turns harmful. One project studies how glia trim synapses, the connections between neurons, as experience shapes brain circuits. The other asks whether sensors that normally detect viral or bacterial DNA and RNA wrongly trigger inflammation in microglia that are clearing debris. This can happen in diseases that strip away myelin, the insulating coating on nerve fibers, such as multiple sclerosis (MS).
Why it matters
In MS and other neurodegenerative diseases, therapies are being designed to boost the clearance of cell debris, which is usually assumed to calm inflammation. Finding that debris-sensing eTLRs block myelin repair could change how such therapies are designed and reveal new targets. Learning why some synapses are removed while others are spared could also help explain abnormal synapse loss in schizophrenia, Alzheimer's disease, and neurodevelopmental disorders.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Dandan Sun
University of Pittsburgh, PA·Neuroscience
Determine how deleting Nhe1, an acid-exporting membrane protein, only in microglia changes phagocytosis-related gene expression and debris clearance after ischemic stroke, using Cx3cr1-CreER;Nhe1 conditional knockout mice.
William S Talbot
Stanford University, CA·Neuroscience
Determine how newly identified positive and negative regulators of myelination control the wrapping of nerve fibers by oligodendrocytes during development, neural plasticity and remyelination, using zebrafish genetics and cellular analysis.
Benjamin Singer
University of Michigan, MI·Neuroscience
Determine whether sepsis combined with presymptomatic amyloid deposition increases complement-driven neuroinflammation and synapse loss in 5xFAD mice, measuring microglial activation, engulfment of synapses, and synaptic transmission.
The school
University of Massachusetts Chan Medical School: 29 labs on PI Pages, $350M a year on research, 55 research doctorates a year.
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